Neurophysins, the intraneuronal peptides which are synthesized with the hormones of the posterior pituitary, oxytocin and vasopressin, have proven to be a major secretory product of the neurophyophysis. This new measure of posterior pituitary function has been applied to the study of human physiology and pathology. We have developed specific radioimmunoassays for two neurophysins in the human, and demonstrated independent secretion of each. Studies during this grant award have proven that one neurophysin is a vasopressin-neurophysin and the second is an oxytocin-neurophysin. Secretion of vasopressin and vasopressin-neurophysin are being investigated during diseases which are associated with abnormal water balance. We have studied hyponatremia after subarachnoid hemorrhage and have shown that the elevated levels of vasopressin may be secondary to volume depletion. A monkey model of subarachnoid hemorrhage will investigate whether the vascular insult is a primary stimulus to natriuresis with secondary elevation of ADH. We have proven that estrogen is a stimulus for the secretion of oxytocin-neurophysin and now have proven concurrent secretion of oxytocin. Oxytocin may have some function at mid menstrual cycle when estrogen levels are elevated. We have begun studies to identify precursors of neurophysins in norman human and rat pituitary and in tumors which synthesize vasopressin. This is a comprehensive study of the anatomy, pathology, physiology and pathophysiology of all of the known peptides which are secreted by the neurohypophysis.